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Research ArticleNEUROPHARMACOLOGY

Long-Lasting Facilitation of 4-Amino-n-[2,3-3H]butyric Acid ([3H]GABA) Release from Rat Hippocampal Slices by Nicotinic Receptor Activation

Attila Köfalvi, Beáta Sperlágh, Tibor Zelles and E. Sylvester Vizi
Journal of Pharmacology and Experimental Therapeutics November 2000, 295 (2) 453-462;
Attila Köfalvi
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Beáta Sperlágh
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Tibor Zelles
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E. Sylvester Vizi
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Abstract

In this study we explored the effect of the stimulation of nicotinic acetylcholine receptors located on interneurons by measuring 4-amino-n-[2,3-3H]butyric acid ([3H]GABA) release and monitoring [Ca2+]i in superfused hippocampal slices. In the presence of 6-cyano-7-nitroquinoxaline-2,3-dione, (±)-2-amino-5-phosphonopentanoic acid, and atropine, i.e., under the blockade of N-methyl-d-aspartate and non-N-methyl-d-aspartate glutamate and muscarinic receptors, nicotine did not alter the spontaneous outflow of [3H]GABA, but significantly increased the stimulation-evoked [3H]GABA efflux. This effect of nicotine depended on the time interval between nicotine treatment and electrical stimulus, the concentration of nicotine (1–100 μM), and the parameters of electrical depolarization. Acetylcholine (0.03–3 mM), and the α7 subtype-selective agonist choline (0.1–10 mM), also potentiated stimulus-evoked release of [3H]GABA, whereas 1,1-dimethyl-4-phenilpiperazinium iodide failed to increase the tritium outflow significantly. The effect of nicotine treatment was prevented by tetrodotoxin (1 μM) and by the nicotinic acetylcholine receptor antagonist mecamylamine (10 μM), and the α7 subtype-selective antagonists α-bungarotoxin (100 nM) and methyllycaconitine (10 nM), whereas dihidro-β-erythroidine (20 nM) was without effect. Perfusion of 100 μM nicotine caused a [Ca2+]itransient in about one-third of the tested interneurons; however, the response to subsequent electrical stimulation remained unchanged. Inhibition of the GABA transporter system by nipecotic acid (1 mM) or by decreasing the bath temperature to 12°C abolished completely the effect of nicotine to potentiate the stimulation-evoked release of GABA. These findings indicate that the activation of α7-type nicotinic receptors of hippocampal interneurons results in a long-lasting ability of these cells to respond to depolarization with an increased release of GABA mediated by the transporter system.

Footnotes

  • Send reprint requests to: Beáta Sperlágh, Institute of Experimental Medicine, Hungarian Academy of Sciences, P.O. Box 67, Budapest, H-1450, Hungary. E-mail: sperlagh{at}koki.hu

  • ↵1 This work was supported by a Philip Morris research grant and by the grants of Hungarian Research Foundation (OTKA), and the Hungarian Medical Research Council (ETT). Some information contained in this article was presented in preliminary form at the 29th Annual Meeting of Society for Neuroscience in Miami Beach, Florida (Sperlágh et al., 1999).

  • Abbreviations:
    nAChR
    nicotinic acetylcholine receptor
    ACh
    acetylcholine
    GABA
    γ-aminobutyric acid
    [3H]GABA
    4-amino-n-[2,3-3H]butyric acid
    AP-5
    (±)-2-amino-5-phosphonopentanoic acid
    CNQX
    6-cyano-7-nitroquinoxaline-2,3-dione
    NMDA
    N-methyl-d-aspartate
    DMPP
    1,1-dimethyl-4-phenylpiperazinium iodide
    DHβE
    dihydro-β-erythroidine
    α-BTX
    α-bungarotoxin
    MEC
    mecamylamine
    MLA
    methyllycaconitine
    TTX
    tetrodotoxin
    PKC
    protein kinase C
    S
    stimulation-evoked release
    AUC
    area-under-the-curve
    ACSF
    artificial cerebrospinal fluid
    fura-2/AM
    fura-2 acetoxymethyl ester
    • Received April 3, 2000.
    • Accepted June 27, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 295 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 295, Issue 2
1 Nov 2000
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Research ArticleNEUROPHARMACOLOGY

Long-Lasting Facilitation of 4-Amino-n-[2,3-3H]butyric Acid ([3H]GABA) Release from Rat Hippocampal Slices by Nicotinic Receptor Activation

Attila Köfalvi, Beáta Sperlágh, Tibor Zelles and E. Sylvester Vizi
Journal of Pharmacology and Experimental Therapeutics November 1, 2000, 295 (2) 453-462;

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Research ArticleNEUROPHARMACOLOGY

Long-Lasting Facilitation of 4-Amino-n-[2,3-3H]butyric Acid ([3H]GABA) Release from Rat Hippocampal Slices by Nicotinic Receptor Activation

Attila Köfalvi, Beáta Sperlágh, Tibor Zelles and E. Sylvester Vizi
Journal of Pharmacology and Experimental Therapeutics November 1, 2000, 295 (2) 453-462;
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